Because of progress in supportive therapies, the upper limit of age for conventional allogeneic stem cell transplantation (allo-SCT) is rising. We retrospectively evaluated the impact of age on transplant outcomes in patients older than 50 years of age who underwent conventional allo-SCT in 8 institutions in Japan. The median age was 52-years old (range 50 to 65). The underlying diseases included severe aplastic anemia (n=3), acute myelogenous leukemia (n=20), acute lymphoblastic leukemia (n=10), chronic myelogenous leukemia (n=11), myelodysplastic syndrome (n=18), and non-Hodgkin lymphoma (n=3). Forty two patients (67%) with hematological malignancies received allo-SCT in an advanced disease stage at the time of transplant. The two-year overall survival and disease-free survival rate were 50.1% and 43.6%, respectively. In patients with hematological malignancies, the two-year probability rates of survival were 54.3% with standard risk patients, and 45.9% with poor risk patients. The severity of acute GVHD, the kind of grafts, and age (≥55) were related to poor prognosis. Our data suggest that prophylaxis of acute GVHD and selection of the graft is more important for older patients, and that patients less than 55-years old can be candidates for conventional allo-SCT.

View full abstract

Twelve transfusion-dependent patients with myelodysplastic syndrome (MDS) were treated with immunosuppressive therapy; 8 with cyclosporin A (CyA), 3 with CyA and antithymocyte globulin (ATG), one with ATG. G-CSF was combined in 10 patients. Eight patients who consisted of 4 treated with CyA, 3 with ATG/CyA, and one with ATG, achieved transfusion-independence. Responses were observed in 8/9 patients with refractory anemia, 0/3 patients with refractory anemia with excess of blast, although the recovery was incomplete in most cases. All of the CyA-responsive patients took drug-dependent courses. The presence of GPI-anchored protein-deficient granulocytes (CD11b+CD55-CD59-) was examined by flow cytometry after treatment in 6 responsive patients, and was demonstrated in 2 of them. HLA-DR15 was found in 5 of 7 responsive patients, suggesting that the presence of this allele may be associated with a good response to immunosuppressive therapy. All responsive patients had refractory anemia classified to IPSS Int-1, and had common conditions as follows: absence of chromosomal abnormality, short interval from diagnosis to therapy, and employment of ATG therapy.

View full abstract

A 70-year-old man was referred to our hospital in March 2001 for the purpose of evaluation for anemia and thrombocytopenia. Physical examination revealed hepatosplenomegaly, normal skin, and normal neurologic findings. Blood examination showed a white blood cell count of 10900/μl, with a differential count of 58.5% eosinophils and 3.5% blast cells. Flow cytometric analysis of eosinophils revealed that they were positive for CD33, CD13, CD25, and HLA-DR. Bone marrow aspiration could not be performed due to dry tap, and bone marrow core biopsy specimen revealed severe myelofibrosis with blastoid cells proliferation. Cytogenetic analysis of bone marrow cells showed isochromosome 17. FISH analysis using a RARα probe (17q21.1) demonstrated 62% of peripheral blood nucleated cells having three signals. BCR/ABL gene rearrangement by FISH analysis was not observed. Allergic disease, infectious disease, parasitic disease, collagen vascular diseases, pulmonary disease, and neoplastic disorders were excluded. Therefore, a diagnosis of chronic eosinophilic leukemia was made. The patient had no symptoms of hypereosinophilia. However, eosinophils with sparse granulation, positivity for CD25, elevated serum levels of soluble IL-2 receptor, and elevated serum levels of eosinophil cationic protein suggested activation of eosinophils. Further analysis is needed regarding the activation of eosinophils in chronic eosinophilic leukemia.

View full abstract

We treated two chronic phase chronic myelogenous leukemia patients with imatinib mesylate. Hematological complete remission and significant regression of bone marrow fibrosis were observed in both patients. The large amount of TGF-β produced by increased bone marrow megakaryocytes might have caused the myelofibrosis, and it was revealed that imatinib mesylate brought about regression of the myelofibrosis by reducing the number of megakaryocytes in both patients.

View full abstract

We investigated changes in various serum cytokines in a case of systemic lupus erythematosus (SLE) accompanied by hemophagocytic syndrome (HPS). The patient, a 15-year-old male, presented in December 1998 with bilateral salivary gland swelling and a history of fever continuing for more than 10 days. After admission, cerebellar ataxia and clouding of consciousness developed. Laboratory examinations revealed leukopenia, thrombocytopenia, high serum LDH and ferritin, hypercytokinemia, and prominent hemophagocytosis in the bone marrow. Given these findings and positive titers of antinuclear antibody, hypocomplementemia, proteinuria and pericarditis, a diagnosis of HPS with associated SLE was made. The patient was treated with high dose methylprednisolone followed by oral prednisolone and cyclosporine. The patient's clinical symptoms, abnormal blood and urine laboratory data consequently improved, and no recurrence of the symptoms has been documented. However, hemophagocytosis in bone marrow recurred with concomitantly increased serum levels of IL-6 and IL-1β. This case indicated that aberrant production of these inflammatory cytokines might be involved in HPS in autoimmune disease.

View full abstract

A 59-year-old man with a six-month history of chronic myelomonocytic leukemia (CMML) was admitted to the Kitasato University Hospital because of melena in September 2000. Colonofiberscopy and barium enema demonstrated an ulcerated tumorous lesion in the transverse colon. The histopathologic findings of the ulcer bed revealed diffuse infiltration of granulocytes at each stage of differentiation. The diagnosis of granulocytic sarcoma (GS) was made. Surgical resection was not indicated, because thrombocytopenia was hardly improved enough to allow surgery despite repetitive transfusion of platelet concentrates. CMML developed to refractory anemia with excess of blast in transformation in February 2001. Two courses of low dose cytarabine plus aclarubicin were ineffective on the GS in spite of a decrease in the peripheral blood blasts. Progression to acute myeloid leukemia eventually broke out, in July 2001. The patient died of leukemia complicated with pneumonia and intestinal obstruction. At present, nine cases of GS in the colon have been reported. However, these cases did not include CMML. This is the first report describing GS in the colon associated with CMML.

View full abstract

A 61-year-old male visited his doctor in October 2000 because of a high fever. Laboratory examination revealed leukocytosis with blast-like cells and thrombocytopenia. He was referred and admitted to our hospital in November 2000. Although he had mild splenomegaly, he had no lymphadenopathy on the first admission. The white blood cell count was 10,520/μl with 45% blast-like cells and the platelet count was 51×10³/μl. Bone marrow aspiration revealed 82% blast-like cells, which were positive for CD5, CD10, CD13, CD19, and CD20. Immunohistochemistry of the bone marrow clot sections revealed blast-like cells were positive for CD5, but negative for TdT, CD23 and cyclin D1. We diagnosed the patient as having de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) with leukemic dissemination. He obtained a complete remission after two courses of CHOP therapy. The third chemotherapy was postponed because of strangulation of the intestine. He relapsed and died in spite of the third chemotherapy. CD5-positive DLBCL is one of the established disease entities that requires an appropriate therapy regimen because it is characterized by elderly onset, extranodal involvement, and a poorer prognosis.

View full abstract

A 24-year-old Japanese male was admitted to our hospital because of lymphadenopathy in his left neck. He had a nine-year history of chronic renal failure, and had received an ABO-mismatched renal allograft and splenectomy in August 2000 after one year of hemodialysis treatment. After renal transplantation, he was treated with FK506, methylprednisolone (mPSL), and mycophenolate mofetil (MMF) as an immunosuppressants for his graft maintenance. On admission, April 2001, he underwent lymphadenectomy, and the immunohistochemical studies revealed that the tumor cells expressed EBV-LMP and EBNA-2 antigens with the histology of diffuse large B-cell lymphoma. Our diagnosis was an Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD), and we reduced the dose of immunosuppressive agents and treated the patient with rituximab. In this case, there may have been two principal risk factors associated with PTLD: first, the patient was treated with higher levels of immunosuppressive agents because of the ABO-mismatched transplantation, and second, he was an EBV-seronegative recipient at the time of pretransplantation.

View full abstract

A 71-year-old man visited our hospital complaining of fever and a bleeding tendency. The peripheral blood WBC count was 10,400/μl with 90% promyelocytes. The bone marrow was hypercellular with 88% promyelocytes. Disseminated intravascular coagulation was recognized. The patient was diagnosed as having acute promyelocytic leukemia and was treated with daily oral administration of all-trans retinoic acid (ATRA) (45 mg/m²/day) and cytarabine (160 mg/day, intravenous drip infusion for the initial five days). The ATRA treatment induced leukemic cells to undergo mature myeloid differentiation. On day 24 after the start of treatment, the WBC count rapidly increased and acute myocardial infarction appeared, with consciousness disturbance and bilateral Babinski reflex appearing three hours later. Magnetic resonance imaging showed a fresh lacunar infarction of the right lenticular nucleus, and serum levels of IL-6 and PAI-1 were found to be elevated at the onset of infarction. Since there was a possibility that the retinoic acid syndrome (RAS) might have helped bring about the infarctions, we stopped the ATRA treatment and started administration of methyl-prednisolone (500 mg/body/day for 3 days) and gabexate mesilate. The WBC count decreased immediately and the consciousness disturbance improved. In this case, ATRA treatment might have initiated the RAS and resulted in some endothelial damage, thus causing the infarctions.

View full abstract

Ten patients with acute myelogenous leukemia or high risk myelodysplastic syndrome who had achieved complete remission following treatment with the CAG regimen were monitored for peripheral blood WT1 expression mRNA levels. Induction therapy with the CAG regimen did not seem to be enough to lower WT1 expression levels to the normal range. In comparison with patients who received intensive chemotherapy for post-remission therapy, those who received only CAG therapy showed higher levels of WT1 expression and more easily relapsed. These data suggest that CAG therapy alone might not be sufficient to maintain complete remission and WT1 monitoring could be useful in the choice of appropriate post-remission therapy after achieving remission with the CAG regimen.

View full abstract

We report a patient with myelodysplastic syndrome (MDS) overt leukemia who developed an acute myeloid leukemia (AML) in donor cells shortly after bone marrow transplantation (BMT) from his HLA-matched sibling. Molecular analysis using microsatellite repeats by polymerase chain reaction proved the new leukemia to be of donor cell origin. The patient received chemotherapy with idarubicin and ara-C, but he died due to mucormycosis.

View full abstract